JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

October 2022

I-P01 

 

Signalment (JPC# 1823588):  Age and breed unspecified, horse

 

HISTORY:  This horse had generalized dermatitis. Several randomly scattered nodular cutaneous lesions were also present in and around the cervical region.

 

MICROSCOPIC DESCRIPTION:  Haired skin, site not specified: Multifocally within the superficial and deep dermis, predominantly surrounding blood vessels and adnexa, there are variably sized nodular aggregates composed of numerous eosinophils, some lymphocytes, plasma cells, and histiocytes, rare multinucleated giant cells, and fewer mast cells. Within the nodules and surrounding dermis, there are numerous tangential and longitudinal sections of microfilariae scattered throughout areas of dermal inflammation; microfilariae are 3-4µm wide with a thin cuticle and are filled with myriad 1x2µm basophilic nuclei. The overlying epidermis is moderately hyperplastic with moderate orthokeratotic hyperkeratosis. 

 

MORPHOLOGIC DIAGNOSIS:  Haired skin, site not specified:  Dermatitis, perivascular and periadnexal, eosinophilic and lymphohistiocytic, subacute, multifocal, moderate, with numerous dermal microfilariae, breed unspecified, equine

 

ETIOLOGY:  Onchocerca sp. (most likely Onchocerca cervicalis)

 

ETIOLOGIC DIAGNOSIS:  Cutaneous onchocerciasis

 

GENERAL DISCUSSION: 

• Onchocerca spp. are filarial nematodes that principally affect horses but can also infect cattle, canids, and other mammals worldwide; cause cutaneous and ocular lesions; incidence has greatly decreased with the use of avermectins 
  • O. cervicalis – horses; worldwide
  • O. reticulata – horses; Europe and Asia
  • O. gutturosa – horses and cattle; N. America, Africa, Australia, Europe
  • O. gibsoni – cattle; Africa, Asia, Australia 
  • O. lienalis – cattle; Australia, North America (potentially ≈ O. gutturosa)
  • O. lupi – dogs, cats, humans; Asia, Southwestern US
  • O. volvulus – humans; causes River Blindness
• Most horses are asymptomatic; prevalence increases with age (>4 years); only certain horses develop clinical signs 
• The presence of microfilariae does not necessarily confirm the diagnosis of cutaneous onchocerciasis; they may be found in the skin of clinically normal horses and in lesions from any equine dermatosis
• Previously thought to cause fistulous withers, poll evil, and recurrent equine uveitis, but no longer associated with these diseases

 

PATHOGENESIS:

• Microfilaria sucked up by blood-sucking intermediate hosts (Simuliidae spp. black flies, gnats, Culicoides spp. biting midges), 
• Develop from microfilarid to L3 larvae in intermediate host, 
• Transferred to new host where L3 migrates through SQ tissues, adults encyst near connective tissues, generate microfilaria that migrate through SQ tissue back to the skin; not through the blood stream as other filarids do
• Cutaneous lesions thought to be due to type I and type III hypersensitivity reactions to antigens from dead and dying microfilariae or to arthropod bites
• Ocular lesions due to aberrant migration of microfilaria 
• Inflammatory response partly due to presence of Wolbachia spp. bacteria (as with other filarids)

 

TYPICAL CLINICAL FINDINGS:

• Incidence of O. cervicalis in clinically asymptomatic horses in endemic areas was 25–100% (before widespread avermectin [ivermectin] use)
• Adult filarids generally do not cause clinical signs; microfilariae are responsible for the ocular and cutaneous lesions, and are usually seen in older horses
• Pruritus is mild to severe
• Non-seasonal

 

TYPICAL GROSS FINDINGS:

• Adults are found encased in nodular, fibrotic, caseous, and calcifying lesions
  • O. cervicalis – funicular portion of ligamentum nuchae over shoulder and neck
  • O. reticulata – tissue of tendon sheaths adjacent to carpus or suspensory ligaments, fetlock
  • O. gutturosa – lamellar part of ligamentum nuchae
• Microfilaria localize along the ventral midline (especially near umbilicus), face, base of mane, proximal forelimbs, pectoral region
• Cutaneous lesions:  Patchy alopecia, erythema, scaling, depigmentation; the presence of a pigmented circular area (“bull’s eye”, annular lesion) or plaques in the center of the forehead is highly suggestive of the disease
• Ocular lesions:  Uveitis, conjunctivitis, keratitis, depigmentation of lateral limbus 

 

TYPICAL MICROSCOPIC FINDINGS:

Nematode:

• Adult Onchocerca sp.:  
  • Filarid nematodes have characteristic very small intestine on cross-section (the most important diagnostic feature of filarids)
  • Microfilariae within the uterus of adult female worms
  • Polymyarian-coelomyarian musculature often becomes atrophied and replaced by hypodermis, thus in cross-section there is an outer cuticle with inner hypodermal layer (unique to Onchocerca sp.)
  • Females have cuticular rings or annulations that encircle the worm and thus appear as cuticular bumps in longitudinal section (unique to Onchocerca sp.)
• Microfilariae (all filarid species): Cuticle, appear to lack musculature, and are filled with myriad 1x2µm basophilic nuclei (“bag of nuclei”)

 

Cutaneous lesions:

• Adult filarid nematodes are typically found in tangled masses in discrete nodules of dense connective tissue within deep subcutaneous tissues, ligaments, and aponeurosis 

• Microfilaria:

• Dead microfilaria induce a pyogranulomatous reaction with marked fibrosis and mineralization 
• Microfilaria are found in nests and pockets in the dermis just under the epidermis and adjacent to adnexal structures; sparse to abundant numbers
• Mononuclear and eosinophilic perivascular dermatitis
• No correlation between number of microfilaria and severity of lesions

 

Ocular lesions: dogs, cats, horses

• Dogs/cats: Adults worms; conjunctival or episcleral inflammatory nodules, exophthalmos, eosinophilic and granulomatous inflammation, fibrosis 
• Horses: Microfilaria; eosinophilic and granulomatous conjunctivitis and peripheral stromal keratitis, uveitis

 

DIFFERENTIAL DIAGNOSIS: 

For gross findings:

• Fly bite dermatoses
• Dermatophytosis
• Sarcoptic mange, psoroptic mange
• Pelodera dermatitis (strongyle)
• Trombiculiasis
• Atopy

 

For histologic findings: 

• Dirofilaria spp. filariasis in dogs/cats. 
• Stephanofilaria spp. and Setaria spp. in cattle

 

COMPARATIVE PATHOLOGY: 

• Cattle
  • Onchocerca gutturosa:  Connective tissue adjacent to nuchal ligament and fascia adjacent to bones in limbs 
  • O. gibsoni (Africa, Asia, Australia):  Brisket, stifle, hip; 2-9cm SQ nodules. Economically significant due to time required for trimming nodules out of carcasses(Mauldin, et al, Jubb, Kennedy,and Palmer’s Pathology of Domestic Animals 2016)
  • O. lienalis (Australia, North America) (may be same species as O. gutturosa): gastrosplenic ligament and splenic capsule
• Sheep: Elaeophora schneideri adults damage leptomeningeal arteries of domestic sheep, microfilaria cause dermatosis, retinal and nasal/oral mucosal irritation. 
• Canids:  Considered an abnormal host for this parasite; O. lupi reported to cause granulomatous nodules in the eye, periocular tissues, and skin

 

REFERENCES:

1. Cooper BJ, Valentine BA. Muscle and tendon. In: Maxie MG, ed. Jubb, Kennedy,and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 247.
2. Gardiner CH, Poynton SL. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology;  2006: 3, 35, 38.
3. Labelle P. The Eye. In: In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1407-1408.
4. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 687-8.
5. Rooney JR. Eyes and ears. In: Rooney JR, ed. Equine Pathology. 1st ed. Ames, IA: Iowa State University Press; 1996: 125-126,162, 294-295.
6. Scott DW, Miller WH.  Parasitic Diseases. In: Equine Dermatology. 2^nd ed. Maryland Heights, MO: Elsevier; 2011:242-245.
7. Valenciano AC, Cowell RL, Young KM. In: Cowell and Tyler's Diagnostic Cytology and Hematology of the Dog and Cat. St. Louis, MO: Elsevier; 2020:159.
8. Welle MM, Linder KE. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1184.
9. Wilcock BP, Njaa BL. Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 452.
10. Zarfoss MK, Dubielzig RR, Eberhard ML, Schmidt KS.  Canine ocular onchocerciasis in the United States: Two new cases and a review of the literature.  Veterinary Ophthalmology. 2005: 8:51-57. 

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